JPH01172356A - Production of dihalogenopropionic acid or derivative thereof - Google Patents

Abstract

PURPOSE:To obtain the title compound useful as an intermediate for agricultural chemicals and drugs readily, in high selectivity and in high yield, by reacting an acrylic acid with a halogen by using a tertiary amine as a catalyst. CONSTITUTION:An acrylic acid shown by formula I [R1-R2 are H, halogen, (substituted)alkyl or (substituted)phenyl; R4 is H, (substituted)alkyl or (substituted)phenyl or a derivative thereof is reacted with a halogen such as Cl2 gas in the molar ratio of 1:0.1-1:100 in a solventless state or in an inert organic solvent such as CCl4 in the presence of a tertiary amine or tertiary phosphine and a polymerization inhibitor such as hydroquinone at -70-100 deg.C for 2-20hr to give the aimed compound shown by formula II (X is halogen). Pyridine or triethylamine is preferably used as the tertiary amine and triphenylphosphine or triethylphosphine as the tertiary phosphine.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to a novel production method for producing dihalogenopropionic acid or its derivatives with good selectivity and high yield.

[Prior art and problems to be solved by the invention] Dihalogenopropionic acid or its derivatives are useful compounds that can be widely used as intermediates for agricultural chemicals and medicines.

Conventional methods for producing dihalogenopropionic acid or its derivatives include chlorinating or brominating methyl acrylate in a methanol solvent to produce methyl 2,3-dichloropropionate or methyl 2,3-dibromopropionate. Method of obtaining esters [Journal of Oz American Chemical Society (J, Am.

Chem.
Method for obtaining 3-substituted dihalogenopropionic acid or derivatives thereof by halogenation (JP-A-56-87531)
etc. are publicly known.

However, the former method has a low yield of 85-88%, and the latter method produces 3 which is more halogenated than the target product.
-Substituted-trihalogenoacrylic alcohol or its derivatives,
Approximately 10% of 3-fl-converted-tedrava p-genoacrylic acid or its derivative was produced as a by-product, and the yield was approximately 80 to 90%, leaving room for improvement in selectivity.

[Means to solve the problem]

The present inventors have investigated an industrial method for producing dihalogenopropionic acid or a derivative thereof with high yield and high selectivity by reacting acrylic acid or a derivative thereof with a halogen. As a result, they discovered that dihalogenopropionic acid or its derivatives can be produced in high yield, with almost no by-products, and with high selectivity when a tertiary amine or tertiary phosphine is used, and the present invention has been completed. I ended up letting it happen.

That is, the present invention is based on the general formula (1) (where RR and R8 represent a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted phenyl group, and R6 represents a hydrogen atom). atom, substituted or unsubstituted furkyl group, substituted or unsubstituted phenyl group) and a halogen in the presence of a tertiary amine or tertiary phosphine. Characterized by general formula (2) (where R, R2 and R8 are hydrogen atoms, halogen atoms, substituted or unsubstituted furkyl groups, substituted or unsubstituted phenyl groups, and R6 is hydrogen atoms, substituted or unsubstituted phenyl groups) represents a furkyl group, a substituted or unsubstituted phenyl group, and X represents a halogen atom).

One of the raw materials used in the present invention is general 2 (11 R, Co, R.

(However, RRR and R4 have the same meanings as above.) It is acrylic acid or a derivative thereof represented by: In the above general formula (11), the number of carbon atoms in the furkyl group represented by R, R, R8, and R6 is not particularly limited, and a linear or branched saturated group may be used. In general, a furkyl group having 1 to 6 carbon atoms is preferred because it is easy to handle. Specific examples of the alkyl group that are generally most preferably used include a methyl group and an ethyl group.

Examples include n-propyl group, 1so-propyl group, n-butyl group, 1so-butyl group, t-butyl group, n-pentyl group, n-hexyl group, and the like. Further, in the general formula, the halogen atoms represented by R1, R, and R8 are fluorine.

Mention may be made of chlorine, bromine or iodine. Further, the substituent of the substituted furkyl group is not particularly limited, and any substituent that is inactive in the reaction system can be used without any restriction. Specific examples of the substituents that can be particularly preferably used include: p-gen atom; methoxy group, ethoxy group, n-propoxy group, is.

-Flukoxy groups such as p-boxy group and n-butoxy group; methylthio group, ethylthio group, n-propylthio group, n-
Examples include furkylthio groups such as butylthio groups; phenyl groups: phenoxy ring groups. Furthermore, the substituent of the substituted phenyl group is not particularly limited, and any substituent that is inactive in the reaction system can be used without any restriction. Particularly preferably used substituents include a halogen atom; a methyl group, an ethyl group, and an n-propyl group.

Alkyl groups such as 1so-propyl group, n-butyl group, 1so-butyl group, t-butyl group; pp methyl group, difluoromethyl group, trifluoromethyl group, trichloromethyl group, trifluoroethyl group, pentafluoroethyl group A herogenofurkyl group such as a phenyl group and the like can be mentioned.

More specific examples of acrylic acid or its derivatives that can be particularly preferably used in the present invention include acrylic acid, acrylic acid methyl ester, and acrylic 1! ! t-Butyl ester, acrylic acid phenyl ester, 3-methyl acrylic acid methyl ester, 3,3-dimethyl acrylic acid ethyl ester, 3-ethyl acrylic acid, 3-phenylacrylic acid phenyl ester, 3-phenyl-3- Methyl acrylic acid ethyl ester, 2-chloroacrylic acid methyl ester.

3-phenyl-2-fluoroacrylic acid methyl ester, 2-methylacrylic acid methyl ester, 2-iso-
Propylacrylic acid, 3-trichloromethyl-2-t-
Butyl acrylic powder butyl ester, 3-n-hexyl-
2-iodoacrylic acid propyl ester, 3-penta-
2-ditylthiomethylacrylic acid is.

-propyl ester, 3.3-dimethyl-2-bromoacrylic acid t-gtyl ester, 3.3-dichloroacrylic acid methyl ester, 3-chloroI:l-2-methoxymethylacrylic acid n-hexyl ester, 3- n-propoxymethyl-2-methylacrylic acid phenyl ester.

3-phenoxy-2-methy7. /thiomethylacrylic acid methyl ester, 3-methyl-2-p-clophenyl acrylic acid methyl ester.

3-p-methylphenylacrylic acid methyl ester, 3
-(o,p-dichlorophenyl)-2-short methyl acrylic methyl ester, 3,3-dimethyl-2-p
-t-butylphenyl acrylic acid ethyl ester, 3-
7'lomomethyl-2-iso-propoxymethylacrylic acid methyl ester, 3-pentafluoroethyl-2-
Methyl acrylic acid methyl ester, 3-diphenyl-3
-Methyl-2-fluoroacrylic acid methyl ester, 2
, 3.3-trimethylacrylic acid methyl ester, 3-
Phenyl-3-methyl-2-ripp acrylic? ! 1t-
, methyl ester, 3-phenyl-3-methylthiomethyl-2-fluoroacrylic acid methyl ester, and the like.

The other raw material used in the present invention is halogen. The halogens include fluorine and chlorine.

Examples include bromine and iodine, with chlorine and bromine being particularly preferred.

The tertiary amine or tertiary bosphine used in the present invention exhibits a catalytic effect during the reaction between the raw materials. The third
The class amine or tertiary phosphine is not particularly limited, and known compounds can be used. Specific examples of particularly preferably used tertiary amines include trimethylamine, triethylamine, tripropylamine, tributylamine,
pyridi]/, pyrazine, and the like. In particular, handling ~・
Triethylamine and pyridine are preferably used because of their ease of application. Further, specific examples of tertiary phosphine that are particularly preferably used include trimethylphosphine, triethylphosphine, triphenylphosphine, and the like. Among these, triethylphosphine and triphenylphosphine are preferably used because of their ease of handling.

In the production of dihalogenopropionic acid or its derivatives according to the present invention, the reaction can be carried out without a solvent or in an inert organic solvent. The inert organic solvent is not particularly limited, and any known inert organic solvent can be used. Particularly preferred examples of inert organic solvents include halogenated hydrocarbon solvents such as methylene chloride, methylene bromide, chloroform, carbon tetrachloride, dichloroethane, and trichloroethane; methanol, ethanol, and propylene chloride; Alcohol solvents such as tools; Aromatic solvents such as benzene, toluene, and xylene; Saturated aliphatic solvents such as pentane, hexane, and heptane; Ether solvents such as diethyl ether, dibutyl ether, dimethoxyethane, diethylene glycol dimethyl ether, and tetrahydrofuran etc.

When carrying out the present invention, if acrylic acid or a derivative thereof has high polymerizability, it is a preferable embodiment to add a polymerization inhibitor and carry out the reaction. Specific examples of the polymerization inhibitor include hydroquinone, hydroquinone monomethyl ether, t-butylcatefur, and the like.

In addition, when carrying out the present invention, the procedure of reaction operation, ie, acrylic acid or its derivatives.

...The addition layer properties of Rodan 9M polymerization inhibitor, inert organic solvent, and tertiary amine or tertiary phosphine are not particularly limited, but usually acrylic acid or its derivative 1 polymerization inhibitor and tertiary phosphine are added. It is preferable to prepare a primary amine or a tertiary phosphine in an inert organic solvent, and blow or drop a halogen into the mixture, or drop a solution of a predetermined amount of a halogen in an inert solvent.

The molar ratio of acrylic acid or its derivative to halogen used in the present invention is not particularly limited, but is generally 1:0, 1 to 1:100, preferably 1:0.
It is preferable to use the ratio in the range of 1.0 to 1:10.

In addition, the amount of tertiary amine or tertiary phosphine to be used is not specifically determined and may be determined as necessary, but
Generally 0.01 for acrylic acid or its derivatives
-80 mole percent, preferably L<1 to 40 mole percent.

Furthermore, when a polymerization inhibitor is used, the polymerization inhibitor is preferably selected in the range of 0.01 to 80 mol percent, preferably 1 to 40 mol percent, based on acrylic acid or its derivative. .

Furthermore, when an inert organic solvent is used, the weight ratio of acrylic acid or its derivative to the inert solvent is generally selected within the range of 1=1 to 1:20°, preferably 1:1 to 1:8. suitable.

In the present invention, the reaction temperature is not particularly limited and can be selected within a wide temperature range, but it is generally suitable to select from the range of -70°C to 100°C, preferably from the range of -20°C to 50°C. In addition, the reaction time varies depending on the reaction conditions, but is usually 2~
20 hours, preferably 4 to 12 hours is suitable.

The method for purifying dihalogenopropionic acid or its derivative obtained in the present invention is not particularly limited. Generally, the reaction solution is added to water, followed by benzene, toluene, and methylene chloride.

It can be purified by extraction with an inert solvent such as chloroform, carbon tetrachloride, ether, etc., drying, and distillation under normal pressure, distillation under reduced pressure, recrystallization, or chromatography.

〔effect〕

The present invention can produce dihalogenopropionic acid or its derivatives in high yield and with good selectivity.

In order to explain the present invention more specifically, reference examples and examples will be given and explained, but the present invention is not limited to these examples.

Reference Example: 86.09 p of acrylic acid methyl ester in a 200 catfish-brown three-necked flask equipped with a stirrer.

21.3 g of dihydrogen phosphate (IJum) and 0.11 g of Hydrogen Phosphate were added, and the mixture was placed in a constant temperature bath at 10°C. chlorine gas at 55M1/m under stirring in a nitrogen atmosphere
After bubbling for an hour, the mixture was further stirred for 1 hour. The reaction solution was then distilled under reduced pressure, but the desired 2,3-dichloropropion-derived methyl ester could only be obtained in an isolated yield of about 80%. In fact, the reaction mixture solution was mixed with 5g-3 of filler.
0 (trade name), when measured at a column temperature of 70"C, only the peak of the target product, 2,3-dichloropropion methyl ester, was observed; however, when the column temperature was 170"
The further chlorinated product, 2, when measured at °C,
2.3-) Dichloropropion-brewed methyl ester and 2
．． 2,3.3-tetracopar propionic acid methyl ester was produced at a ratio of 2,1 to 101C of 2,3-dichloropropionyl methyl ester, which was the target product.

Example 1 In a 200D brown three-necked flask equipped with a stirrer, 86.09. ! i+.

Pyridine 1.63.9 and hydroquinone 0.1/l
was added and placed in a constant temperature bath at 30°C. In a nitrogen atmosphere,
After stirring, chlorine gas was blown in at a rate of 55 d/m for 7 hours, and the mixture was further stirred for 1 hour. Subsequently, the reaction solution was distilled under reduced pressure to obtain the target product, 2,3-dichloropropion-rich methyl ester (boiling point: 80°C/3 mHl), at a concentration of 156.1,9. Obtained with a yield of 99.4%.

Example 2 In the same manner as in Example 1, 2-chloroacrylic acid methyl ester (121N),) ethylamine (1.52.9%) and hydroquinone (0.9%) were added. In the presence of II, chlorine gas was blown into the reactor to cause a reaction. After performing similar processing, the target objects 2, 2.
3-) +7 chloropropionic acid methyl ester (boiling point 90"C/27fiH&) 119.9p, yield "$99
．． Obtained at 1%.

Example 3 In the same manner as in Example 1, 3-methylacrylic acid ethyl ester 114,9. )+7 phenylphosphine 3.93
．． li' and hydroquinone 0. Il, meta/-l 10
In the presence of 0d, chlorine gas was blown into the reactor to cause a reaction. Subsequently, methanol was distilled off under reduced pressure, water was added, and the mixture was extracted with chloroform. By drying the chloroform layer and distilling it off under reduced pressure, 2,3-dichlorobutyric acid ethyl ester with a purity of 99.5% or more was obtained in a yield of 99.5%.

Example 4 In a 500-1 brown three-necked flask equipped with a stirrer, 148. S+.

1.77 g of triethylphosphine, 0.1 g of noioid p-quinone, and 200,111 tons of carbon tetrachloride were added, and the mixture was placed in a constant temperature bath at 30°C. Bromine 160I under stirring in nitrogen atmosphere
was gradually added dropwise. The reaction was stopped 5 hours after the dropwise addition. The reaction solution was washed with water, dried, and evaporated under reduced pressure to obtain the desired 2,3-diglomoprobion phenyl ester with a purity of 99.5% and a yield of 99.3%.

Example 5 Using the raw materials, halogen, catalyst and solvent shown in Table 1,
Dihalogenopropion Kuma or its derivatives were synthesized in the same manner as in Example 1 under the reaction conditions shown in Table 1. The yield of the resulting product is also shown in Table IK.

Claims (1)

[Claims] General formula (1) ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (1) (However, R_1, R_2 and R_3 are hydrogen atoms, halogen atoms, substituted or unsubstituted alkyl groups, substituted or unsubstituted represents a substituted phenyl group, and R_4 represents a hydrogen atom, a substituted or unsubstituted alkyl group, or a substituted or unsubstituted phenyl group. General formula (2) characterized by reacting in the presence of class phosphine ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (2) (However, R_1, R_2 and R_3 are hydrogen atoms, halogen atoms, substituted or unsubstituted R_4 represents a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted phenyl group, and X represents a halogen atom. A method for producing an acid or its derivative.